This proposal requests funds to purchase a nanoComputed Tomography system (nanotom(R);phoenix|x- ray, marketed by GE Healthcare) with the intent of significantly advancing the research programs of over a dozen federally funded investigators at the Mount Sinai School of Medicine. This technology will facilitate our ability to accurately and efficiently quantify aspects of the 3D arrangement or distribution of tissues that are important for assessing functional outcomes and for studying the pathogenesis of disease. For musculoskeletal research, our investigators show that understanding the development of traits during pre- and postnatal growth is central to advancing our understanding of the genetic basis of skeletal fragility and craniosynostosis. However, the growing skeleton remains an extremely challenging structure to image using conventional microCT systems because of the small structural features and low mineralization. Further, researchers conducting large-scale research on the 3D arrangement of trabeculae in human bone and whale bone are limited to low resolution CT images or 2D histology, neither of which will advance their programs. For cardiovascular research, efforts to use nanoparticles to identify the spatial distribution of macrophages within cardiovascular tissues are currently limited to a rabbit model because we lack an available high resolution imaging system to move this research to the mouse model. Consequently, our investigators must rely on destructive, time-consuming, and expensive histological methods to acquire data. Although histology provides valuable cellular information, the structural readouts are limited to 2D information, and thus impair our ability to acquire the 3D spatial information needed to advance our scientific programs. Our investigators need an extremely versatile, multi-scale imaging system to generate high resolution 3-dimensional (3D) images of skeletal and cardiovascular structures ranging in size from 1- 100 mm. We propose to purchase the phoenix|x-ray nanotom(R) because this system is a unique ex vivo computed tomography system that non-destructively acquires extremely high resolution (0.5 mm) 3D images of x-ray attenuating samples. The nanotom can operate in four modes, including a nanofocus mode (0.5mm voxel size) for small biological samples (e.g., postnatal mouse bone) and a high power mode (180kV, 15 Watts) for large biological specimens (e.g., proximal human femora). This single system will allow us to do multi-scale imaging and to offset the heavy demand placed on our existing and aging microCT system. These two systems will be incorporated into a Shared Research Facility to better support the imaging needs of MSSM researchers. Relevance: The non-destructive imaging and accurate quantification provided by the phoenix|x-ray nanotom(R) allows specimens to be used for subsequent analyses such as histomorphometry and biomechanics, providing a more complete characterization than otherwise possible. Public Health Relevance: This proposal is a request to purchase a phoenix|x-ray nanotom(r), a uniquely versatile imaging system that will enhance our scientific research program by obtaining 3D images of biological structures at sub-micron resolution from which our users can quantify traits leading to a better understanding of functional outcomes and the pathogenesis of musculoskeletal and cardiovascular diseases. This multi-scale imaging system will be incorporated into a Shared Resource Facility to make it available to the Mount Sinai research community. The nanotom will provide state-of-the-art high resolution multi-scale imaging capabilities that will enhance collaborations among investigators at our institution and identify connections to diseases and treatments that would otherwise have been overlooked.